scholarly journals Downregulated Platelet miR-1233-5p in Patients with Alzheimer’s Pathologic Change with Mild Cognitive Impairment is Associated with Aβ-Induced Platelet Activation via P-Selectin

2020 ◽  
Vol 9 (6) ◽  
pp. 1642
Author(s):  
Bo Kyung Lee ◽  
Min Hee Kim ◽  
Sang Yoon Lee ◽  
Sang Joon Son ◽  
Chang Hyung Hong ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cell Adhesion ◽  
Mild Cognitive Impairment ◽  
Expression Profiles ◽  
Human Platelets ◽  
Pathologic Change ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
Mirna Expression Profiles

MicroRNAs (miRNAs) have been proposed as a promising biomarker for various diseases including Alzheimer’s disease (AD). More attention has recently been focused on the diagnosis and treatment at earlier stage of mild cognitive impairment (MCI) for preventing its progression to AD. To identify potential pathologic markers for Aβ(+)MCI (Alzheimer’s pathologic change with MCI), we investigated miRNA expression profiles in the platelets from patients with Aβ(+)MCI, in comparison with those from Aβ(−)MCI (Non-Alzheimer’s pathologic change with MCI) and CNI (cognitively normal individuals). We found that let-7i-5p, miR-125a, miR-1233-5p, and miR-6787-5p were significantly downregulated, while miR-6880-5p expression was upregulated. Of these, only miR-1233-5p was significantly downregulated by Aβ treatment in both human platelets and their precursor megakaryocytes (MEG-01 cells). We explored the role of miRNAs by using miRNA mimics or inhibitors, and found that the diminished level of miR-1233-5p was associated with Aβ-induced increase in the expression of P-selectin and cell adhesion to fibronectin. Our results further indicated that Aβ-induced increase in platelet/MEG adhesion to fibronectin is likely mediated via P-selectin. In conclusion, this study suggests the downregulation of platelet-derived miR-1233-5p as a pathologic marker for Aβ(+)MCI.

scholarly journals Lower functional hippocampal redundancy in mild cognitive impairment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stephanie Langella ◽  
◽  
Muhammad Usman Sadiq ◽  
Peter J. Mucha ◽  
Kelly S. Giovanello ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Resting State ◽  
Memory Performance ◽  
Potential Mechanism ◽  
Network Efficiency ◽  
Cognitively Normal ◽  
Normal Individuals ◽  
The Relationship

AbstractWith an increasing prevalence of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in response to an aging population, it is critical to identify and understand neuroprotective mechanisms against cognitive decline. One potential mechanism is redundancy: the existence of duplicate elements within a system that provide alternative functionality in case of failure. As the hippocampus is one of the earliest sites affected by AD pathology, we hypothesized that functional hippocampal redundancy is protective against cognitive decline. We compared hippocampal functional redundancy derived from resting-state functional MRI networks in cognitively normal older adults, with individuals with early and late MCI, as well as the relationship between redundancy and cognition. Posterior hippocampal redundancy was reduced between cognitively normal and MCI groups, plateauing across early and late MCI. Higher hippocampal redundancy was related to better memory performance only for cognitively normal individuals. Critically, functional hippocampal redundancy did not come at the expense of network efficiency. Our results provide support that hippocampal redundancy protects against cognitive decline in aging.

scholarly journals Evaluation of Imaging Windows for Tau PET Imaging Using 18F-PI2620 in Cognitively Normal Individuals, Mild Cognitive Impairment, and Alzheimer’s Disease Patients

2020 ◽  
Vol 19 ◽  
pp. 153601212094758 ◽  
Author(s):  
Chanisa Chotipanich ◽  
Monchaya Nivorn ◽  
Anchisa Kunawudhi ◽  
Chetsadaporn Promteangtrong ◽  
Natphimol Boonkawin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Standardized Uptake Value ◽  
Brain Regions ◽  
Post Injection ◽  
Cognitively Normal ◽  
Scanning Time ◽  
Normal Individuals

Background: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) patients, using 18F-PI 2620 dynamic PET acquisition. Methods: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic 18F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions. Results: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of 18F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups. Conclusion: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

scholarly journals The Association Between the Number of Neuropsychological Measures and the Base Rate of Low Scores

Assessment ◽  
2019 ◽  
pp. 107319111986464 ◽  
Author(s):  
Javier Oltra-Cucarella ◽  
Miriam Sánchez-SanSegundo ◽  
María Rubio-Aparicio ◽  
Juan Carlos Arango-Lasprilla ◽  
Rosario Ferrer-Cascales
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Base Rate ◽  
Z Score ◽  
Expected Number ◽  
Cognitively Normal ◽  
Neuropsychological Measures ◽  
Normal Individuals

Obtaining one or more low scores, or scores indicative of impairment, is common in neuropsychological batteries that include several measures even among cognitively normal individuals. However, the expected number of low scores in batteries with differing number of tests is unknown. Using 10 neuropsychological measures from the National Alzheimer’s Coordinating Center database, 1,023 permutations were calculated from a sample of 5,046 cognitively normal individuals. The number of low scores (i.e., z score ≤−1.5) varied for the same number of measures and among different number of measures and did not increase linearly as the number of measures increased. According to the number of low scores shown by fewer than 10% of the sample, cognitive impairment should be suspected for 1 or more, 2 or more, and 3 or more in batteries with up to 2 measures, 3 to 9 measures, and 10 measures, respectively. These results may increase the identification of mild cognitive impairment.

scholarly journals Characterising mild behavioural impairment in Asian mild cognitive impairment and cognitively normal individuals

2020 ◽  
Vol 16 (S6) ◽  
Author(s):  
Fennie Wong ◽  
Kok Pin Ng ◽  
Chathuri Yatawara ◽  
Audrey Low ◽  
Zahinoor Ismail ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitively Normal ◽  
Normal Individuals

Ethnic Differences Between Hispanics and Non-Hispanic Whites in Neuropsychiatric Symptoms Predict Conversion to Mild Cognitive Impairment

2020 ◽  
pp. 089198872095708
Author(s):  
Bhaskar Thakur ◽  
Luis Alvarado ◽  
Christopher Dodoo ◽  
Ricardo Salazar ◽  
Alberto J. Espay ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Ethnic Differences ◽  
Primary Outcome ◽  
Neuropsychiatric Symptoms ◽  
Data Driven ◽  
Cognitively Normal ◽  
Physical Behavior ◽  
Normal Individuals ◽  
Normal Cognition

The aim of the study is to ascertain the neuropsychiatric symptoms (NPS) subtypes significantly influencing progression to mild cognitive impairment (MCI) by ethnicity. In this retrospective cohort study, we included 386 cognitively normal individuals participating in the longitudinal Texas Alzheimer’s Research and Care Consortium between February 2007 and August 2014. The primary outcome was time to incident MCI. Data driven NPS subtypes at baseline were identified and the effects of these subtypes on the outcome were obtained for Hispanic and non-Hispanic ethnic cohorts and summarized with a hazard ratio (HR). Three NPS subtypes were identified and internally validated: psychomotor apathy factor (including agitation, irritability, apathy), affective mood factor (including depression, anxiety), and physical behavior factor (including nighttime behavior, eating/appetite disturbances). In adjusted analysis, a psychomotor apathy score of NPS was the best predictor for MCI (HR = 2.19, p = 0.037) among non-Hispanics whereas physical behavior score was the most predictive of MCI (HR = 2.55, p = 0.029) among Hispanics. A high score of affective mood factor also tended to increase the risk of MCI (HR = 2.09, p = 0.06) in Hispanics. Progression from normal cognition to MCI was differentially predicted by NPS subtypes in Hispanics and non-Hispanic whites. These data may inform the allocation of efforts for monitoring individuals at-risk of MCI.

scholarly journals Association Between Amyloid-β, Small-vessel Disease, and Neurodegeneration Biomarker Positivity, and Progression to Mild Cognitive Impairment in Cognitively Normal Individuals

2019 ◽  
Vol 74 (11) ◽  
pp. 1753-1760 ◽  
Author(s):  
Neelesh K Nadkarni ◽  
Dana Tudorascu ◽  
Elizabeth Campbell ◽  
Beth E Snitz ◽  
Annie D Cohen ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Community Dwelling ◽  
Small Vessel ◽  
Study Endpoint ◽  
Cognitively Normal ◽  
Vessel Disease ◽  
Normal Individuals

Abstract Background: We estimated the prevalence and incidence of amyloid-β deposition (A), small-vessel disease (V), and neurodegeneration (N) biomarker positivity in community-dwelling cognitively normal individuals (CN). We determined the longitudinal association between the respective biomarker indices with progression to all-cause mild cognitive impairment (MCI) and its amnestic and nonamnestic subtypes. Methods: CN participants, recruited by advertising, underwent brain [C-11]Pittsburgh Compound-B (PiB)-positron emission tomography (PET), magnetic resonance imaging, and [F-18]fluoro-2-deoxy-glucose (FDG)-PET, and were designated as having high or low amyloid-β (A+/A−), greater or lower white matter hyperintensities burden (V+/V−) and diminished or normal cortical glucose metabolism (N+/N−). MCI was adjudicated using clinical assessments. We examined the association between A, V, and N biomarker positivity at study baseline and endpoint, with progression to MCI using linear regression, Cox proportional hazards and Kaplan–Meier analyses adjusted for age and APOE-ε4 carrier status. Results: In 98 CN individuals (average age 74 years, 65% female), A+, V+, and N+ prevalence was 26%, 33%, and 8%, respectively. At study endpoint (median: 5.5 years), an A+, but not a V+ or N+ scan, was associated with higher odds of all-cause MCI (Chi-square = 3.9, p = .048, odds ratio, 95% confidence interval = 2.6 [1.01–6.8]). Baseline A+, V+, or N+ were not associated with all-cause MCI, however, baseline A+ (p = .018) and A+N+ (p = .049), and endpoint A+N+ (p = .025) were associated with time to progression to amnestic, not nonamnestic, MCI. Conclusion: Longitudinal assessments clarify the association between amyloid-β and progression to all-cause MCI in CN individuals. The association between biomarker positivity indices of amyloid-β and neurodegeneration, and amnestic MCI reflects the underlying pathology involved in the progression to prodromal Alzheimer’s disease.

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